Poly-(D,L-lactic acid) microspheres incorporating histological dyes for intra-pulmonary histopathological investigations

Polylactic acid (PLA) microspheres incorporating fluorescein as a histological marker have been prepared and used as a model for the testing of inhaled PLA microspheres (2-5 mu m) in the lung. PLA microspheres (20 mg) were delivered to rabbits in the form of a saline nebulization. The distribution pattern within the pulmonary system showed that the fluorescein-labelled microspheres were distributed about the four lobes in discrete groups. The comparative numbers of these groups showed a trend towards a reduced concentration in the lower lobes. Subsequent histological examination revealed that the microsphere-treated lungs had been significantly damaged after 24 h. Histological damage was assessed in terms of pulmonary haemorrhage, eosinophilia and neutrophil infiltration.